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INNOSC Theranostics and
Pharmacological Sciences MDD biomarkers: Clinical implications

Table 5. Significant lncRNA related to MDD
Expression Utility Signaling pathway References
Downregulated Diagnostic marker (upregulated Synaptic plasticity 39
gsk3βAS1 post-treatment)
Downregulated Diagnosis and treatment Ribosome activities, Alzheimer’s disease, RNA 71
TCONS_00019174 response degradation, pancreatic cancer, Parkinson’s
ENST00000566208 disease, cell cycle, DNA replication, prostate
NONHSAG045500 cancer, Huntington’s disease and long-term
ENST00000517573 depression
NONHSAT034045
NONHSAT142707
Upregulated Diagnosis and severity Gene regulation 73
Y5, MER11C, PCAT1, PCAT29
Downregulated Diagnosis, severity, and Wnt signaling pathway 39
gsk3βAS1 [ENST00000482027], treatment response (upregulated
gsk3βAS2 [ENST00000491262] post-treatment)
gsk3βAS3 [BC035247]
Downregulated Diagnostic and severity Gene regulation 73
RMRP assessment
Downregulated Diagnosis Cellular pathways 71
TCONS_00019174
Upregulated Diagnosis CC chemokine receptor activity and 47
ENSG00000229807.1_2 cytokine-cytokine receptor interactions and T
ENSG00000234449.2_1 cell receptor
ENSG00000205663.5_1
ENSG00000271964.1_2
ENSG00000279995.1_2
ENSG00000271109.1_1
ENSG00000205662.2_1
ENSG00000244620.1_1
ENSG00000204282.4_2
ENSG00000225938.1_1
Downregulated
ENSG00000273295.1_1
ENSG00000218537.1_1
ENSG00000271869.1_1
Abbreviation: MDD: Major depressive disorder.
An et al. investigated DE of circRNAs among patients of (cg06642177), have been implicated in MDD. DGKH and
MDD and type II diabetes and reported that the following SGK1 are specific for bipolar disorder whereas the GSK3B
circRNAs were exclusively and significantly expressed is specific for MDD. Clive et al. worked on validating their
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in MDD, summarized in Table 6. Yu et al. documented previously identified biomarker – spindle and kinetochore-
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that circHIPK2 expression was significantly enhanced associated protein (SKA2) – which predicts suicide risk and
(AUC = 0.796) in MDD individuals and it is highly specific post-traumatic stress disorder (PTSD). DNA methylation
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for diagnosing and predicting MDD l. 77 of SKA2 revealed three probes (cg08469255, cg22029879,
and cg24437859) that were significantly correlated with
4.1.5. DNA methylation in MDD the biosignature for DNA methylation-based suicidal
Numata et al. explored the role of DNA methylation in behavior prediction. Powel et al. investigated IL-11 gene-
diagnosing MDD using blood samples. A multiplex related DNA methylation across the CpG island and
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DNA methylation profile, predominantly from gene its role in predicting MDD treatment response in the
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promoter regions within CpG islands, demonstrated 100% GENDEP clinical trial. In the same clinical trial, the role
sensitivity and specificity as a diagnostic biomarker for of IL-11 transcriptional differences and the associated
MDD. Among 313 differentially methylated CpG sites in single nucleotide polymorphism (SNP), rs1126757, in
the CGIs in the gene promoter regions, several genes, such predicting MDD treatment response was also determined.
as DGKH (cg00109274), GSK3B (cg14472315), and SGK1 DNA methylation in the IL-11 gene has thus proved to

Volume 8 Issue 2 (2025) 39 doi: 10.36922/itps.4404